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Introduction <p>The associations between lipid levels and atrial fibrillation (AF) remain inconsistent, and whether functional status modifies these relationships is unclear. In this prospective cohort study, the joint associations of grip strength, lipid levels, and lipid-related genetic risk with incident AF were evaluated.</p> Methods <p>A prospective cohort analysis was conducted, and Cox models were used to evaluate the associations of lipid levels, lipid-related polygenic risk scores (PRSs), and grip strength with incident AF. Joint exposure categories were constructed according to lipid status (normal vs. elevated) and grip strength level (normal vs. reduced) to compare AF risk across different combinations. Age-stratified analyses were further conducted to examine age-related heterogeneity. Interaction terms between lipid levels and grip strength were included to test interaction and assess the effect modification of grip strength on the lipid-AF association. Participants receiving lipid-lowering therapy at baseline were excluded in sensitivity analyses.</p> Results <p>Lipid levels, lipid-related PRSs, and grip strength were each associated with incident AF. In joint exposure analyses, individuals with both elevated lipid levels and reduced grip strength had a lower risk of AF than those with elevated lipids but normal grip strength in the overall population [HR 0.925 (0.889, 0.961)]. However, among participants younger than 55 years, the coexistence of elevated lipids and reduced grip strength was associated with a higher risk compared with having either abnormality alone. Interaction analyses demonstrated significant relations between low-density lipoprotein (LDL) levels, LDL-PRS, and grip strength, indicating that the latter significantly modified the association between lipids and AF. When grip strength was below 41.53&#xa0;kg for LDL, below 48.90&#xa0;kg for total cholesterol, and within 17.07–36.11&#xa0;kg for triglycerides, elevated lipid levels were linked to a reduced risk of AF; this association gradually attenuated and became non-significant as grip strength increased.</p> Conclusions <p>This study found that grip strength significantly modified the associations of lipid levels and lipid-related genetic risk with AF, with evident age-related heterogeneity. In individuals younger than 55 years, effective lipid management and improving muscle strength may help reduce the risk of AF.</p>

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Joint associations of grip strength, lipid levels, and lipid-related genetic risk with atrial fibrillation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月9日

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  • Zihao Zhang,
  • Jianfeng Huang,
  • Xu Wang,
  • Qing Li,
  • Yirong Yang,
  • Kuan Ning,
  • Yifan Wang,
  • Tanxiu Chen,
  • Rui Xiong,
  • Xinjie Liu,
  • Shaolie Huang,
  • Lijuan Deng,
  • Pingping Shen,
  • Yian Zhan,
  • Shanhua Xiao,
  • Wen-Quan Zou

摘要

Introduction

The associations between lipid levels and atrial fibrillation (AF) remain inconsistent, and whether functional status modifies these relationships is unclear. In this prospective cohort study, the joint associations of grip strength, lipid levels, and lipid-related genetic risk with incident AF were evaluated.

Methods

A prospective cohort analysis was conducted, and Cox models were used to evaluate the associations of lipid levels, lipid-related polygenic risk scores (PRSs), and grip strength with incident AF. Joint exposure categories were constructed according to lipid status (normal vs. elevated) and grip strength level (normal vs. reduced) to compare AF risk across different combinations. Age-stratified analyses were further conducted to examine age-related heterogeneity. Interaction terms between lipid levels and grip strength were included to test interaction and assess the effect modification of grip strength on the lipid-AF association. Participants receiving lipid-lowering therapy at baseline were excluded in sensitivity analyses.

Results

Lipid levels, lipid-related PRSs, and grip strength were each associated with incident AF. In joint exposure analyses, individuals with both elevated lipid levels and reduced grip strength had a lower risk of AF than those with elevated lipids but normal grip strength in the overall population [HR 0.925 (0.889, 0.961)]. However, among participants younger than 55 years, the coexistence of elevated lipids and reduced grip strength was associated with a higher risk compared with having either abnormality alone. Interaction analyses demonstrated significant relations between low-density lipoprotein (LDL) levels, LDL-PRS, and grip strength, indicating that the latter significantly modified the association between lipids and AF. When grip strength was below 41.53 kg for LDL, below 48.90 kg for total cholesterol, and within 17.07–36.11 kg for triglycerides, elevated lipid levels were linked to a reduced risk of AF; this association gradually attenuated and became non-significant as grip strength increased.

Conclusions

This study found that grip strength significantly modified the associations of lipid levels and lipid-related genetic risk with AF, with evident age-related heterogeneity. In individuals younger than 55 years, effective lipid management and improving muscle strength may help reduce the risk of AF.